Lamivudine, chemically, (2R-cis)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(IH)-pyrimidinone; (−)-2′-deoxy-3′-thiacytidine; (−)-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cystosine; or 3TC is a reverse transcriptase inhibitor. The therapeutic uses of lamivudine and related compounds and their preparations were disclosed in WO 91/17159.
Lamivudine is also useful in the treatment of hepatitis B infection as disclosed in U.S. RE39155. WO Patent Publication No. 92/20344 disclosed a method of treatment of HIV infection and other viral infection with lamivudine in combination with other antiviral agents such as Zidovudine, chemically 3′-azido-3′-deoxythymidine.
Lamivudine is commercially available as 100 mg, 150 mg and 300 mg tablets; 10 mg/ml in 240 ml oral solution. It is sold under the name EPIVIR.
U.S. Pat. No. 5,905,082 reported that the needle shaped crystals of form I are not favored for pharmaceutical formulation into solid dosage forms because of poor flow characteristics.
WO Patent Application Publication No. 2009/031026 described a novel pharmaceutical composition of lamivudine and cyclodextrin complex.
EP Patent No. 1,180,033 disclosed lamivudine, lactose, starch, crystalline cellulose, hydroxypropyl cellulose and talc in pharmaceutical formulation.
The combination composition of lamivudine and zidovudine is commercially available as 150 mg and 300 mg tablets. It is sold under the name COMBIVIR.
U.S. Pat. No. 6,113,920 disclosed a pharmaceutical composition comprising two active pharmaceutical ingredients namely lamivudine and zidovudine and a pharmaceutically acceptable glidant ingredient in the form of a film coated tablet.
WO Patent Application Publication No. 00/18383 described antiviral combination of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid isopropyl ester and zidovudine and/or lamivudine.
WO Patent Application Publication No. 96/01110 described a combination of zidovudine, lamivudine and loviride for the treatment of HIV infections and AIDS.
WO Patent Application Publication No. 2007/068934 described combination of lamivudine with tenfovir disoproxil fumarate.
Lamivudine exhibits polymorphism. Form I and Form II are reported in U.S. Pat. No. 5,905,082, Form III are disclosed in WO 2007/119248.
All the above mentioned patents are incorporated by references.
In spite of all the above disclosed formulations of lamivudine, still there is a need for pharmaceutical formulations that have good flow properties, good compressibility and stability in terms of polymorphic form during and after formulation.
Thus an object of the present invention is to provide a pharmaceutical formulation containing lamivudine, having good flow properties, good compressibility and bulk density, all of which enable a formulation that can be produced without any difficulty.
Another object of the present invention is to provide the oral tablet formulation of lamivudine with isomalt as filler, the oral solid pharmaceutical formulation being capable of avoiding capping of lamivudine with any polymorphic forms.
Another object of the present invention provides a process for preparing of lamivudine and/or in combination with other anti-Human immunodeficiency virus (anti-HIV) agents.
Another object of the present invention is to provide a pharmaceutical formulation of lamivudine in combination with other anti-HIV agents, having good flow properties, good compressibility and bulk density, which enable a formulation that can be produced without any difficulty.
Another object of the present invention is to provide suitable pharmaceutical formulation of lamivudine and/or in combination with other anti-HIV agents.
Yet, another object of the present invention is to provide stable oral dosage forms of lamivudine.